538 research outputs found

    Recovered Memory: Kindly \u27Daughters Of Maine\u27 Nursed Bodies And Souls

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    Driving north from Boston on the way to Southwest Harbor, Maine, I always slow for an intersection outside Ellsworth, familiar now through many summers, where Route 1 joins the road from Blue Hill to form a tree-shaded oasis, remote from the stream of eastbound traffic. Guarding this little park sta...

    The Larynx as a Musical Instrument

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    Cerebral Light

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    A gene regulatory network armature for T lymphocyte specification

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    Choice of a T lymphoid fate by hematopoietic progenitor cells depends on sustained Notch–Delta signaling combined with tightly regulated activities of multiple transcription factors. To dissect the regulatory network connections that mediate this process, we have used high-resolution analysis of regulatory gene expression trajectories from the beginning to the end of specification, tests of the short-term Notch dependence of these gene expression changes, and analyses of the effects of overexpression of two essential transcription factors, namely PU.1 and GATA-3. Quantitative expression measurements of >50 transcription factor and marker genes have been used to derive the principal components of regulatory change through which T cell precursors progress from primitive multipotency to T lineage commitment. Our analyses reveal separate contributions of Notch signaling, GATA-3 activity, and down-regulation of PU.1. Using BioTapestry (www.BioTapestry.org), the results have been assembled into a draft gene regulatory network for the specification of T cell precursors and the choice of T as opposed to myeloid/dendritic or mast-cell fates. This network also accommodates effects of E proteins and mutual repression circuits of Gfi1 against Egr-2 and of TCF-1 against PU.1 as proposed elsewhere, but requires additional functions that remain unidentified. Distinctive features of this network structure include the intense dose dependence of GATA-3 effects, the gene-specific modulation of PU.1 activity based on Notch activity, the lack of direct opposition between PU.1 and GATA-3, and the need for a distinct, late-acting repressive function or functions to extinguish stem and progenitor-derived regulatory gene expression

    Notch/Delta signaling constrains reengineering of pro-T cells by PU.1

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    PU.1 is essential for early stages of mouse T cell development but antagonizes it if expressed constitutively. Two separable mechanisms are involved: attenuation and diversion. Dysregulated PU.1 expression inhibits pro-T cell survival, proliferation, and passage through β-selection by blocking essential T cell transcription factors, signaling molecules, and Rag gene expression, which expression of a rearranged T cell antigen receptor transgene cannot rescue. However, Bcl2 transgenic cells are protected from this attenuation and may even undergo β-selection, as shown by PU.1 transduction of defined subsets of Bcl2 transgenic fetal thymocytes with differentiation in OP9-DL1 and OP9 control cultures. The outcome of PU.1 expression in these cells depends on Notch/Delta signaling. PU.1 can efficiently divert thymocytes toward a myeloid-like state with multigene regulatory changes, but Notch/Delta signaling vetoes diversion. Gene expression analysis distinguishes sets of critical T lineage regulatory genes with different combinatorial responses to PU.1 and Notch/Delta signals, suggesting particular importance for inhibition of E proteins, Myb, and/or Gfi1 (growth factor independence 1) in diversion. However, Notch signaling only protects against diversion of cells that have undergone T lineage specification after Thy-1 and CD25 up-regulation. The results imply that in T cell precursors, Notch/Delta signaling normally acts to modulate and channel PU.1 transcriptional activities during the stages from T lineage specification until commitment

    Competition and collaboration: GATA-3, PU.1, and Notch signaling in early T-cell fate determination

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    T-cell precursors remain developmentally plastic for multiple cell generations after entering the thymus, preserving access to developmental alternatives of macrophage, dendritic-cell, and even mast-cell fates. The underlying regulatory basis of this plasticity is that early T-cell differentiation depends on transcription factors which can also promote alternative developmental programs. Interfactor competition, together with environmental signals, keep these diversions under control. Here the pathways leading to several lineage alternatives for early pro-T-cells are reviewed, with close focus on the mechanisms of action of three vital factors, GATA-3, PU.1, and Notch-Delta signals, whose counterbalance appears to be essential for T-cell specification

    Management of Glaucoma in Pregnancy

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    Management of glaucoma during pregnancy represents a challenge for the physician. Important disease and patient health decisions begin even prior to conception and continue throughout pregnancy and breastfeeding. Data on this topic is limited due to ethical and legal constraints and challenges of conducting large, prospective, and randomized clinical trials on this patient population. Our review suggests that individually, intraocular pressure is lower in a pregnant woman when compared to a non-pregnant woman. Importantly, the medical management of glaucoma during pregnancy poses special challenges due to the possibility of adverse effects of medications on the fetus and newborn. Laser trabeculoplasty and traditional filtration surgery, as well as minimally invasive glaucoma surgery, represent non-drug management options. Thus, managing glaucoma in pregnancy is a delicate balance between treatment to prevent damage to the optic nerve in the mother and avoidance of interventions potentially harmful to the fetus. This literature review of published individual and population-based studies was performed in order to explore current knowledge and guidelines in the management of glaucoma in pregnancy

    From participation to dropout

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    The academic e-learning practice has to deal with various participation patterns and types of online learners with different support needs. The online instructors are challenged to recognize these and react accordingly. Among the participation patterns, special attention is requested by dropouts, which can perturbate online collaboration. Therefore we are in search of a method of early identification of participation patterns and prediction of dropouts. To do this, we use a quantitative view of participation that takes into account only observable variables. On this background we identify in a field study the participation indicators that are relevant for the course completion, i.e. produce significant differences between the completion and dropout sub-groups. Further we identify through cluster analysis four participation patterns with different support needs. One of them is the dropout cluster that could be predicted with an accuracy of nearly 80%. As a practical consequence, this study recommends a simple, easy-to-implement prediction method for dropouts, which can improve online teaching. As a theoretical consequence, we underline the role of the course didactics for the definition of participation, and call for refining previous attrition models
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